To determine whether stem/progenitor cells are present in adult mouse thyroid, we focused on Side Population cells. Side Population cells are characterized by their ability to efflux the vital dye Hoechst 33342 when analyzed by flow cytometry, due to expression of the ATP binding cassette (ABC)-dependent transporter ABCG2, and are highly enriched for stem/progenitor cell activity. SP cells have been identified in various hematopoietic and non-hematopoietic adult tissues, the latter including the liver, skeletal muscle, lung, kidney, and mammary gland. We previously identified Side Population cells in the adult mouse thyroid at approximately 1% of the total population of cells, which highly express ATP binding cassette (ABC)-dependent transporter ABCG2 and the stem cell marker genes encoding nucleostemin and Oct4, but not thyroid differentiation markers such as thyroid peroxidase and thyroglobulin, as examined by real-time polymerase chain reaction. Because of the size of thyroid and the small number of Side Population cells obtainable, we performed partial thyroidectomy on mice in aim to enhance the population of thyroid Side Population cells. This was based on the hypothesis that partial thyroidectomy mimics acute thyroid injury and thyroid stem/progenitor cells may be required to actively participate in the regeneration of injured thyroid. Partial thyroidectomized thyroid returned to the original size after two weeks of thyroidectomy. The phenomenon itself is worth noting since thyroid was considered as an organ that does not return to its full size after partial resection. Partial thyroidectomized thyroids were removed after 2 days of the surgery, and were subjected to flow cytometric analysis. The percentage of Side Population cells increased after partial thyroidectomy, suggesting that stem/progenitor cells in the Side Population cells may be activated by partial thyroidectomy, resulting in the increased population. We are currently carrying out microarray analysis to determine possible marker genes for Side Population cells as compared with non-Side Population cells and those that increase in their population only after partial thyroidectomy. In order to understand the changes that occur after partial thyroidectomy at the morphological and molecular levels, two-weeks post-partial thyroidectomized thyroids have been subjected to histological analysis, electron microscopy, and laser microdissection, followed by microarray analysis. Cells with clear appearance and/or with faintly eosinophilic cytoplasm appeared in partial thyroidectomized thyroids at high levels, which were scarcely observed in normal thyroids. Characterization of these unusual cells and their possible relation to stem/progenitor cells is ongoing.